Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth
In several systems, hydroxyurea has been shown to trigger nitric oxide (NO) release or activation of NO synthase (NOS). To elucidate this duality in its pharmacological effects, during myelosuppression, we individually examined hydroxyurea’s (NO releasing agent) and NO metabolites’ (stable NO degrad...
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2021-10-01
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| author | Tijana Subotički Olivera Mitrović Ajtić Dragoslava Djikić Marijana Kovačić Juan F. Santibanez Milica Tošić Vladan P. Čokić |
| author_facet | Tijana Subotički Olivera Mitrović Ajtić Dragoslava Djikić Marijana Kovačić Juan F. Santibanez Milica Tošić Vladan P. Čokić |
| author_sort | Tijana Subotički |
| collection | DOAJ |
| description | In several systems, hydroxyurea has been shown to trigger nitric oxide (NO) release or activation of NO synthase (NOS). To elucidate this duality in its pharmacological effects, during myelosuppression, we individually examined hydroxyurea’s (NO releasing agent) and NO metabolites’ (stable NO degradation products) effects on erythroid colony growth and NOS/NO levels in mice using NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Hydroxyurea and nitrite/nitrate decreased the bone marrow cellularity that was blocked by PTIO only for the NO metabolites. Hydroxyurea inhibition of colony-forming unit-erythroid (CFU-E) formation and reticulocytes was reversed by PTIO. Moreover, hydroxyurea, through a negative feedback mechanism, reduced inducible NOS (iNOS) expressing cells in CFU-E, also prevented by PTIO. Nitrate inhibition of burst-forming units-erythroid (BFU-E) colony growth was blocked by PTIO, but not in mature CFU-E. The presented results reveal that NO release and/or production mediates the hydroxyurea inhibition of mature erythroid colony growth and the frequency of iNOS immunoreactive CFU-E. |
| first_indexed | 2024-03-10T05:41:42Z |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T05:41:42Z |
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| record_format | Article |
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| spelling | doaj.art-d9113f8dbc9b4b628f010db3de4ea6ef2023-11-22T22:33:00ZengMDPI AGBiomolecules2218-273X2021-10-011111156210.3390/biom11111562Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor GrowthTijana Subotički0Olivera Mitrović Ajtić1Dragoslava Djikić2Marijana Kovačić3Juan F. Santibanez4Milica Tošić5Vladan P. Čokić6Department of Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, SerbiaDepartment of Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, SerbiaDepartment of Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, SerbiaDepartment of Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, SerbiaDepartment of Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, SerbiaDepartment of Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, SerbiaDepartment of Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, SerbiaIn several systems, hydroxyurea has been shown to trigger nitric oxide (NO) release or activation of NO synthase (NOS). To elucidate this duality in its pharmacological effects, during myelosuppression, we individually examined hydroxyurea’s (NO releasing agent) and NO metabolites’ (stable NO degradation products) effects on erythroid colony growth and NOS/NO levels in mice using NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Hydroxyurea and nitrite/nitrate decreased the bone marrow cellularity that was blocked by PTIO only for the NO metabolites. Hydroxyurea inhibition of colony-forming unit-erythroid (CFU-E) formation and reticulocytes was reversed by PTIO. Moreover, hydroxyurea, through a negative feedback mechanism, reduced inducible NOS (iNOS) expressing cells in CFU-E, also prevented by PTIO. Nitrate inhibition of burst-forming units-erythroid (BFU-E) colony growth was blocked by PTIO, but not in mature CFU-E. The presented results reveal that NO release and/or production mediates the hydroxyurea inhibition of mature erythroid colony growth and the frequency of iNOS immunoreactive CFU-E.https://www.mdpi.com/2218-273X/11/11/1562hydroxyureanitric oxideerythroid coloniesnitric oxide synthasenitritenitrate |
| spellingShingle | Tijana Subotički Olivera Mitrović Ajtić Dragoslava Djikić Marijana Kovačić Juan F. Santibanez Milica Tošić Vladan P. Čokić Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth Biomolecules hydroxyurea nitric oxide erythroid colonies nitric oxide synthase nitrite nitrate |
| title | Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth |
| title_full | Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth |
| title_fullStr | Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth |
| title_full_unstemmed | Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth |
| title_short | Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth |
| title_sort | nitric oxide mediation in hydroxyurea and nitric oxide metabolites inhibition of erythroid progenitor growth |
| topic | hydroxyurea nitric oxide erythroid colonies nitric oxide synthase nitrite nitrate |
| url | https://www.mdpi.com/2218-273X/11/11/1562 |
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